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Biomedical subjects

I N Mefford

Publications and source records attributed to I N Mefford.

At least 73 records · Page 4Linked to original sources
PubMed1984

Narcolepsy: cholinergic receptor changes in an animal model.

An inbred colony of narcoleptic doberman pinschers has been analyzed for muscarinic receptor levels in 19 discrete brain regions. In comparison to age-matched controls, receptors were generally elevated in the brainstem and reduced in forebrain areas. No changes in receptor binding affinity were detected. The increased receptor levels found in the brainstem suggest that cholinoceptive neurons in this region are hypersensitive and may be involved in the initiation of cataplexy and other aspects of the narcolepsy syndrome.

Animals↗
PubMed1984

Femtogram detection limits for biogenic amines using microbore HPLC with electrochemical detection.

Detection limits for biogenic amines, serotonin (5-HT), 5-hydroxyindoleacetic acid, 5-hydroxytryptophan, norepinephrine, epinephrine, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), of 50-200 fg are reported. This was accomplished using microbore HPLC with electrochemical detection. Reproducibility at the 1-5 pg level of 1.6-8.1% was obtained. The utility of this approach is demonstrated for analysis of brain tissues of 1 microgram or less.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Day/night differences in pineal indoles in the adult pigeon (Columba livia).

Day/night differences in concentrations of 5-hydroxy and 5-methoxy indole metabolites in the pineal gland of the pigeon are described. A simultaneous determination of 5-hydroxytryptamine (serotonin), 5-hydroxyindoleacetic acid, 5-hydroxytryptophol, N-acetyl-5-hydroxytryptamine (N-acetyl serotonin), 5-methoxyindoleacetic acid, 5-methoxytryptophol, tryptophan, indoleacetic acid and melatonin was accomplished using a recently developed procedure employing high-performance liquid chromatography with electrochemical detection. As in mammalian species, an inverse relationship was observed between N-acetylated indoles and serotonin and its acid metabolites. Melatonin and N-acetyl serotonin were increased approximately three-fold at night to concentrations of 0.730 and 1.79 ng/pineal respectively. Daytime serotonin values were 44.9 +/- 13.0 ng/pineal and decreased to 12.3 +/- 6.5 ng/pineal during the dark phase.

Animals↗
PubMed1983

5-hydroxytryptophan elevates serum melatonin.

Daytime administration of 5-hydroxytryptophan to sheep elevated serum melatonin more than sevenfold within 2 hours. This suggests that administration of 5-hydroxytryptophan could be used as the basis of a clinical test of pineal function and that melatonin might mediate some clinical effects of 5-hydroxytryptophan.

Animals↗
PubMed1983

Narcolepsy: biogenic amine deficits in an animal model.

Concentrations of biogenic amine metabolites in discrete brain areas differed significantly between dogs with genetically transmitted narcolepsy and age- and breed-matched controls. Dopamine and 3,4-dihydroxyphenylacetic acid were consistently elevated in the brains of narcoleptic animals, while homovanillic acid was not. Narcoleptic animals consistently exhibited lower utilization of dopamine and higher intraneuronal degradation of dopamine but no uniform decrease in serotonin utilization. Hence neuropathology appears to be associated with genetically transmitted canine narcolepsy. The data indicate a nonglobal depression of dopamine utilization or turnover or both.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Epinephrine and norepinephrine responses in continuously collected human plasma to a series of stressors.

The present study employed continuous blood withdrawal to examine epinephrine and norepinephrine responses to a cognitive stressor (mental arithmetic), active physical stressors (handgrip and knee bends), passive painful stressors (venipuncture and cold pressor), and a medical procedure that was considered nonstressful (blood pressure measurements). The data were analyzed by analysis of variance (ANOVA) and by time series analysis. The ANOVA indicated that epinephrine and norepinephrine increased significantly in response to the stressors. Epinephrine showed a greater increase to the cognitive stressor than to the others. Time series analysis, however, showed a more varied pattern. It indicated that the height and duration of response differed considerably across subjects and across interventions. The results from both analytic procedures are compared and discussed in terms of current hypotheses of catecholamine response.

Adult↗
PubMed1983

Hyperserotonemia and platelet serotonin uptake and release in schizophrenia and affective disorders.

The authors found that platelet serotonin concentrations were significantly elevated in patients with chronic schizophrenia and in patients with bipolar major depressive disorder. High-affinity serotonin uptake was significantly reduced only in patients with bipolar major depressive disorder. Thrombin-induced release of serotonin from platelets in any patient group was not different from that of normal control subjects. Platelet serotonin storage in chronic schizophrenic patients was also not different from that in normal control subjects. These platelet findings could not be explained by age, sex, or medication variables. The authors suggest that the pharmacodynamics of platelet serotonin may be different in chronic schizophrenia than in bipolar major depressive disorder.

Adult↗
PubMed1983

Reciprocal day/night relationship between serotonin oxidation and N-acetylation products in the rat pineal gland.

Pineal tryptophan, serotonin [5-hydroxytryptamine (5-HT)], N-acetylserotonin, melatonin, 5-hydroxyindoleacetic acid, 5-hydroxytryptophol, 5-methoxytryptophol, and 5-methoxyindoleacetic acid were measured by high pressure liquid chromatography with electrochemical detection. A complete analysis required less than the equivalent of two rat pineal glands. Samples were obtained at eight time points. A reciprocal physiological relationship was found between oxidation and N-acetylation products of 5-HT. 5-HT and the oxidation products 5-hydroxyindoleacetic acid, 5-hydroxytryptophol, 5-methoxytryptophol, and 5-methoxyindoleacetic acid decreased at night, when the N-acetylation products N-acetylserotonin and melatonin increased. These observations are consistent with the hypothesis that circadian changes in the N-acetylation of 5-HT by indoleamine N-acetyltransferase is the major factor controlling circadian changes in the amounts of 5-HT, and 5-HT oxidation and N-acetylation products in the rat pineal gland.

Acetylation↗
PubMed1982

Tyrosine hydroxylase activation. Comparison of in vitro phosphorylation and in vivo administration of haloperidol.

Rat striatal tyrosine hydroxylase (TH) was assayed 2 hr following treatment with 1 mg/kg haloperidol. TH activity in striata from haloperidol-treated rats (haloperidol TH) was increased significantly relative to control when assayed at pH 7.0, but not at pH 6.0, in the presence of 175 muM tetrahydrobiopterin (BH4). TH was also phosphorylated in vitro, catalyzed by sufficient quantities of the catalytic subunit of bovine heart protein kinase to cause greater than 90% activation after 10 min. TH was activated by phosphorylation at both pH 6.0 and pH 7.0, but the activation was greater at pH 7.0. Haloperidol TH, activated relative to control TH at pH 7.0, was activated by phosphorylation, but there was no difference between haloperidol TH and control TH activity at either pH 6.0 or 7.0 following phosphorylation. Comparison of Lineweaver-Burk plots of nonphosphorylated and phosphorylated TH indicated that activation by phosphorylation was due to a 5-fold change in Km for BH4 and a 2-fold change in Vmax at pH 7.0. Haloperidol TH kinetics were intermediate between those of nonphosphorylated and phosphorylated TH at pH 7.0. Analysis by Lineweaver-Burk, Hanes-Woolf, and Eadie-Scatchard plots suggested that the haloperidol TH kinetic data were the result of a mixture of two forms of the enzyme, with different affinities for cofactor. Theoretical calculations of TH activity of mixtures of nonphosphorylated and phosphorylated TH suggested that the haloperidol data could be explained by postulating a mixture of 25-35% phosphorylated TH molecules with 65-75% nonphosphorylated TH molecules. An hypothesis of the role of TH phosphorylation during conditions of increased neuronal firing rate, such as may occur with haloperidol treatment, is presented.

Animals↗
PubMed1982

Distribution of norepinephrine, epinephrine, dopamine, serotonin, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindole-3-acetic acid in dog brain.

The distribution and endogenous concentrations of norepinephrine, epinephrine, dopamine, serotonin, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindole-3-acetic acid were determined in the brains of adult dogs. Norepinephrine and epinephrine were localized primarily in 'central core' areas in brain stem and hypothalamus. Dopamine (DA) and its major metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acids (HVA), were localized primarily in basal ganglia with relatively high concentrations also found in amygdala, septum and substantia nigra. HVA was also found in relatively high concentrations in areas where DA concentrations was very low. Serotonin and 5-hydroxyindole-3-acetic acid levels were highest in brain stem, hypothalamus, globus pallidus and nucleus accumbens. Epinephrine levels were higher than in previously studied species, at times as much as 25-30% of norepinephrine and frequently greater than dopamine in brain stem and hypothalamus. Using the ratios 5-hydroxyindole-3-acetic acid/serotonin and homovanillic acid/dopamine as indicators of serotonin and dopamine turnover and utilization, both putative transmitters were found to be generally more highly utilized in areas of lower concentration, especially in brain stem and cortex. Catecholamines were found to be unconjugated in dog brain. DOPAC and HVA were found to exist primarily in the unconjugated form. DOPAC was found to be slightly conjugated in most areas while 10-20% of HVA was present in the conjugated form in most cases.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Central and peripheral contributions to hypothalamic epinephrine.

Hypothalamic epinephrine concentrations were examined following adrenal demedullation or after surgical hemisection of ascending projections to the hypothalamus. Following surgical transection epinephrine in the ipsilateral hypothalamus was depleted by approximately 60%. Adrenal demedullation had no effect on hypothalamic epinephrine concentrations. It was concluded that hypothalamic epinephrine was central in origin.

Adrenal Medulla↗
PubMed1981

Regional distribution of ascorbate in human brain.

A comprehensive mapping of ascorbate distribution in human brain was carried out by liquid chromatography analysis. The data agree with earlier literature values where comparable and provide new information on several brain regions, including a detailed distribution in the thalamus. While ascorbate concentrations tend to be high in regions rich in catecholamines, there is no real correlation between the two.

Amygdala↗
PubMed1981

In vivo intraneuronal MAO inhibition in rat brain SKF 64139, comparison to other potent PNMT inhibitors.

SKF 64139, a potent inhibitor of adrenal and brain phenylethanolamine-N-methyltransferase (PNMT), was found to have effects on catecholamines, serotonin and their metabolites in rat brain which suggest it may act as a potent inhibitor of monoamine oxidase (MAO) 'in vivo' after acute administration. Evidence of this was obtained by observing the concurrent elevation of serotonin and depletion of its major metabolite 5-hydroxyindoleacetic acid (5-HIAA), as well as depletion of the dopamine metabolites homovanillic acid and 3,4-dihydroxyphenyl-acetic acid (DOPAC) following acute administration. Additional evidence was obtained by antagonism of the increase in acid metabolites and depletion of amines following treatment with reserpine. Using the depletion of brain DOPAC as an index of MAO activity, an ED50 of 3-4 mg/kg was found for SKF 64139 as an "in vivo' MAO inhibitor.

3,4-Dihydroxyphenylacetic Acid↗